Despite advances in systemic therapy, oxygen remains the most potent of all radiation sensitizers, increasing sensitivity by a factor of 3. Oxygen tension varies by individual, by time of day, and by organ being studied. It also is well known that many of the natural (e.g. tumor growth) and therapeutic processes change the pO2 in tumors dynamically and that pO2 in tumors varies among individuals with the same type of tumor in the same stage. The potential gains by making smart, adaptive use of an improved understanding of the oxygen tension within a tumor are enormous. Currently there are no clinical methods to obtain accurate, quantitative measurements of tumor pO2 under treatment conditions. The purpose of this proposal for a PPG is to change this situation, introducing a practical and effective technology to provide a direct, repeatable, quantitative method for clinicians to measure pO2 in tumors and in other tissues. This method is based on EPR oximetry, which has undergone extensive preclinical evaluation as well as feasibility testing in a small set of cancer patients. This method will be able to individualize therapy and validate methods aimed at increasing the pO2 in tumors by radiobiologically significant amounts. The PPG is a collaborative effort of three institutions: Dartmouth which has been the site that has developed clinically applicable EPR oximetry techniques and which has an extensive infrastructure for the development of in vivo EPR instruments and techniques; Brussels which has together with Dartmouth been a very significant source of many of the key preclinical studies demonstrating the effectiveness of EPR oximetry; and Emory University which has a leading academic Radiation Oncology program and has previous and ongoing collaboration with Dartmouth using in vivo EPR system. The PPG is organized in three projects, with each project involving all 3 institutions and utilizing different but complimentary approaches to advance clinical EPR oximetry. The goals of the PPG are to demonstrate that the capability of having a clinically applicable method available for direct and repeated measurements of tumor pO2 has been realized and does indeed provide the types of measurements required to enable clinicians to exploit the enhanced therapeutic opportunities that can be obtained by repeated measurements of pO2. It also will determine the relationships between the quantitative measurements of tumor pO2 by EPR with the indirect but currently more widely available clinical methods used to infer to tumor hypoxia. The success of this PPG will make future clinical trials possible where the information from these measurements is applied to change treatment and the effects on outcomes determined.